The mechanisms that control the release of antidiuretic hormone (ADH) in normal individuals appear to be a complex interplay of osmoreceptor and cardiovascular volume receptor activity. Inferential evidence currently available would suggest that volume or stretch receptors play a prime role in the regulation of blood ADH levels and thus water homeostasis. Manipulations presumed to alter atrial filling, such as positional changes, have been shown to have significant effects on blood ADH levels in normal subjects. The experiments we are pursuing are designed to study the effects of cardiac disease on the volume regulatory mechanisms for ADH release. These studies consist of determining the effect of positional changes on blood ADH levels and renal function in patients with mitral stenosis before, 10 to 12 days post-operative and three to six months following surgical repair. Left atrial pressure is monitored at the time of surgical repair. Patients with right to left and left to right shunts are also studied. These studies should determine if volume regulation of ADH is altered by cardiac disease, and if so, if normal regulation is regained following surgical repair. In addition, information will be gained concerning the role of ADH in edema formation and in post- operative fluid retention. The role of ADH in the production of hyponatremia associated with status asthmaticus is being investigated prospectively. We have evidence that prolactin, or a degradation product of prolactin may have significant antidiuretic and/or naturetic effects. Studies have been initiated to determine if this substance is of importance in water and electrolyte balance in man.